Our study evaluating the accuracy and cost-effectiveness of human papillomavirus (HPV) testing versus Pap smears for primary screening provides a clear understanding of tradeoffs that must be weighed when choosing between these two tests. We found an inverse relationship between sensitivity and specificity. Tests with lower sensitivity, such as Pap smears, had higher specificity, whereas tests for HPV DNA detection had higher sensitivity and lower specificity. While the role of high sensitivity in detecting disease cannot be disputed, when the trade-off is low specificity there is a substantial cost implication, particularly for a screening test that is repeated at regular intervals. Preliminary results from our group suggest that testing for the cyclin-dependant kinase inhibitor, p1 6INK4a provides a more accurate indication of disease status than either Pap or HPV DNA testing. Since p1 6 INK4a is protein there is potential for developing a low cost ELISA assay. A low cost test coupled with a self-collection method may provide a viable screening option for those women who obtain medical services without pelvic exams. During the next funding cycle we propose to define the accuracy and relative cost-effectiveness of pl6rNK4a testing of a clinician-collected sample and HPV DNA testing of a self-collected vaginal swab sample. Results for these two tests will be compared with results for thin-layer Pap and HPV DNA testing of a cervical sample. Since screening is only one component of cervical cancer prevention, we will continue our studies of viral, host and environmental risk factors, paying particular attention to those factors that may be modified through behavior change, or by future immunization strategies. To this end, we plan to more fully elucidate relationships between HPV 16 variants, persistent high levels of E6/E7rnRNA and CIN3. The overall goal of this research is development of accurate and cost-effective cervical cancer prevention strategies that will improve the health of diverse populations.